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. 2001 Feb;2(2):157-64.
doi: 10.1038/84264.

IL-18-stimulated GADD45 beta required in cytokine-induced, but not TCR-induced, IFN-gamma production

J Yang  1 , H Zhu, T L Murphy, W Ouyang, K M Murphy
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IL-18-stimulated GADD45 beta required in cytokine-induced, but not TCR-induced, IFN-gamma production

J Yang (VSports app下载) et al. Nat Immunol. 2001 Feb.

Abstract

Interleukin-12 (IL-12) and IL-18 induce synergistic transcription of interferon gamma (IFN-gamma) that is T cell receptor (TCR)-independent, not inhibited by cyclosporin A and requires new protein synthesis. To characterize this pathway, we screened for genes that are induced in IL-12- and IL-18-treated T helper type 1 cells. GADD45 beta, which activates mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase kinase 4 (MEKK4), was induced by IL-18 and augmented by IL-12. GADD45 beta expression in naïve CD4+ T cells activated p38 MAPK and selectively increased cytokine-induced, but not TCR-induced, IFN-gamma production VSports手机版. Kinase-inactive MEKK4 and inhibition of the p38 MAPK pathway both selectively inhibit cytokine-induced, but not TCR-induced, IFN-gamma production. Thus, the synergy between IL-12 and IL-18 may involve GADD45 beta induction, which can maintain the MEKK4 and p38 MAPK activation that is necessary for cytokine-induced, but not TCR-induced, IFN-gamma production. .

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